Drug-eluting implantable medical devices have become popular in recent times for their ability to perform their primary function (such as structural support of a vessel, for example) and their ability to medically treat the area in which they are implanted.
For example, drug-eluting stents have been used to act as scaffolds to support lumens of vessels in open positions and to prevent restenosis in coronary arteries. Drug-eluting stents may administer therapeutic agents such as anti-inflammatory compounds that block local invasion/activation of monocytes, thus preventing the secretion of growth factors that may trigger vascular smooth muscle cell proliferation and migration. Other potentially anti-restenotic compounds, including antiproliferative agents, may also be administered. Other classes of drugs such as anti-thrombotics, anti-oxidants, platelet aggregation inhibitors and cytostatic agents have also been suggested for anti-restenotic use.
Drug-eluting stents may be coated with a polymeric material which, in turn, is impregnated with a drug or a combination of drugs. Once the stent is implanted at a target location, the drug is released from the polymer for treatment of the local tissues. The drug is released by a process of diffusion through the polymer layer for biostable polymers, and/or as the polymer material degrades for biodegradable polymers.
Controlling the rate of elution of a drug from the drug impregnated polymeric material is generally based on the properties of the polymer material. However, at the conclusion of the elution process, the remaining polymer material in some instances has been linked to an adverse reaction with the vessel, possibly causing a small but dangerous clot to form. Further, drug impregnated polymer coatings on exposed surfaces of medical devices may flake off or otherwise be damaged during delivery, thereby preventing the drug from reaching the target site. Still further, drug impregnated polymer coatings are limited in the quantity of the drug to be delivered by the amount of a drug that the polymer coating can carry and the size of the medical devices. Controlling the rate of elution using polymer coatings is also difficult.
Stents can be manufactured from a variety of materials. These materials include, but are not limited to, metals and polymers. Both metal and polymer vascular stents have been associated with thrombosis, chronic inflammation at the implantation site, and impaired remodeling at the stent site. It has been proposed that limiting the exposure of the vessel to the stent to the immediate intervention period would reduce late thrombosis chronic inflammation and allow the vessel to return to its normal functional state. One means to produce a temporary stent is to implant a bioabsorbable or biodegradable stent.
There are several parameters to consider in the selection of a bioabsorbable material for stent manufacture. These include, but are not limited to, the strength of the material to avoid potential immediate recoil of the vessel, the rate of degradation and corrosion, and biocompatibility with the vessel wall. Additionally, it may be desirable to include therapeutic agents in the bioabsorbable stent such that the therapeutic agent is released at the implantation site during degradation of the stent. The mechanical properties of the stent and release profiles of therapeutic agents directly depend on the rate of degradation of the stent material which is controlled by selection of the stent materials, passivation agents and the manufacturing process of the stent. Currently there are two types of materials, i.e. polymers and metals, used in bioabsorbable stents.
Bioabsorbable polymer stent materials have several significant limitations. Their radial strength is lower than metallic materials, which can result in early recoil post implantation and other mechanical tradeoffs. Also, bioabsorbable polymer stent materials are associated with a significant degree of local inflammation, and they have a relatively slow bioabsorption rate. Additionally, polymeric stents are often radiolucent which impairs accurate positioning within a vessel lumen. The physical limitations of the polymer require thick struts to increase radial strength which impedes their profile and delivery capabilities. Non-biodegradable markers are also needed to provide radiopacity. Metal bioabsorbable stents are attractive since they have the potential to perform similarly to durable metal stents.
There exists a need for a bioabsorbable, drug-eluting stent that incorporates the strength characteristics of a metal with nonpolymer drug eluting properties.